RNA阵列技术检测自发性高血压大鼠甲羟戊酸途径酶的基因表达  

Alterations in gene expression of series key enzymes in mevalonic acid pathway detected by RNA array in spontaneously hypertensive rats

作　　者：李亮[1] 胡申江[1] 董海涛[2] 康兰[1] 陈乃云[1] 方永启[2] 

机构地区：[1]浙江大学医学院第一附属医院心内科,浙江杭州310031 [2]浙江大学生物技术研究所,浙江杭州310029

出　　处：《中国病理生理杂志》2008年第1期54-59,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30470715);国家教育部高等学校博士学科点专项科研基金资助项目(No.20040335118)

摘　　要：目的:探讨甲羟戊酸(MVA)途径的9个酶在不同周龄自发性高血压大鼠(SHR)发病过程中的基因表达变化特点。方法:提取2、4、6、8、10、12不同周龄雄性SHR以及正常血压大鼠(WKY)的心室肌、血管平滑肌、肝脏和肾脏4种组织的总RNA,共294个样品,利用高通量RNA阵列技术(RNA array)检测甲羟戊酸途径的9个酶的基因在不同周龄SHR和WKY大鼠中mRNA表达谱的改变。结果:(1)SHR大鼠从第6周开始收缩压明显高于WKY(P<0.01)。(2)12周龄SHR大鼠体内血清胆固醇浓度明显低于WKY大鼠,组织中的胆固醇浓度没有明显差异(P<0.01)。(3)在SHR大鼠心脏、血管、肝脏、肾脏组织中:MVA中间产物的合成酶如法呢醇焦磷酸合成酶(FDS)、异戊烯化焦磷酸化异构酶(IDI)、法呢醇转移酶α亚基(FT1)和β亚基(FT2)的表达明显高于WKY(P<0.01)。(4)SHR肾脏组织中羟甲基戊二酰辅酶A还原酶(HMGR)、甲羟戊酸激酶(MVK)、焦磷酸甲羟戊酸脱羧酶(MVD)、鲨烯合成酶(SQS)和鲨烯环氧化酶(SQ)表达较为一致,早期(2-4周)SHR大鼠的基因表达明显高于WKY,随着周龄增加SHR的表达进一步增高,且与WKY相比都有明显差异(P<0.01)。(5)在心脏、血管和肝脏中,HMGR、MVK、MVD、SQS和SQ的基因表达无明显规律。结论:SHR大鼠随着周龄的增长甲羟戊酸途径中各酶基因表达的改变,以非胆固醇产物类合成酶(如IDI、FDS和FT1、FT2)表达增加为特点,这一改变是否与高血压有关尚待进一步验证。AIM： To explore the alteration in gene expressions of several enzymes in mevalonic -acid （MVA） pathway in SHR. METHODS： 294 samples of total RNA were extrated from the tissues of ventriculum, aortic smooth muscle, liver and kidney in SHR and WKY. RNA array was used to determine the mRNA level of several enzymes in mevalonic acid pathway. RESULTS： （ 1 ） Systolic blood pressure of SHR surpassed that in WKY since the 6th week （ P 〈 0. 01 ）. （2） The level of cholesterol in serum was significantly lower in SHR than that in WKY （P 〈 0. 01 ）, while that in tissue between two bands had no difference. （3） The gene overexpressions of four enzymes in the four tissues of SHR （P 〈 0. 01 ）, including farnesyl diphosphate synthase （FDS）, isopentenyl diphosphate isomerase （IDI）, farnesyltransferase alpha subunit （ FT1 ）, farnesyltransferase beta subunit （ FT2）, which catalyze the vital mid - productions in MVA pathway, were observed. （4） Gene overexpressions of some enzymes assayed in MVA pathway in SHR renal tissue were observed since 4th week （P 〈 0. 01 ）, including 3 - hydroxy - 3 - methylglutaryl - coenzyme A reductase （ HMGR）, mevalonate kinase （MVK） , mevalonate decarboxylase （MVD） , squalene synthetase （SQS） and squalene epoxidase （SQ）. （5） The gene expressions of these enzymes in ventriculum, aortic smooth muscle and liver showed no difference between two band rats, eg HMGR, MVK, MVD, SQS, SQ. CONCLUSION： The gene expressions of several enzymes in mevalonic acid non- cholesterol pathway in SHR ascend and the mechanism will be further explored.

关 键 词：自发性高血压大鼠 甲羟戊酸途径 基因表达 

分 类 号：R363[医药卫生—病理学]